Glaucoma i a heterogeneous group of diseases which together constitute the second leading cause of blindness among Americans, and the leading cause among African Americans. Yet, little is known about the underlying basis of the disorder. The most common form of glaucoma, known as primary open angle glaucoma, occurs in a setting in which the anatomical structures of the eye appear normal. The long term goal of our research is to understand the mechanisms responsible for causing open angle glaucoma. We have recently identified mutations in a gene, LMX1B, which cause a developmental syndrome known as mail-patella syndrome (NPS) that includes open angle glaucoma as a feature. The LMX1B gene encodes a protein with characteristics of a transcription factor, a protein that turns other genes on or off. A primary goal of the current proposal is to place the LMX1B gene in the context of the genetic regulatory pathways which produce and maintain the normal eye, through identification of gene regulated by LMX1B and protein cofactors which work with it. We will also investigate whether LMX1B, or genes regulated by it, are mutated in the DNA of people with primary open angle glaucoma and may identify new genes responsible for the disease in Americans, ultimately leading to better diagnosis and treatment.